This research is a project that has as a goal, developing a system for the direct injection and targeting of retroviral vectors to specific cell types in vivo. Several approaches designed to achieve the goal of developing an injectable gene therapy vector are being pursued. This projects initial strategy is to study the structure-to-function properties of the envelope protein of murine retroviruses (it is the envelope protein that directs the retrovirus to a particular cell type). Studies underway include; determination of the essential regions for receptor binding in the MMLV gp70 protein, investigating the properties of chimeric MMLV/4070A amphotropic envelopes, and analysis of the resulting host range potentials of hybrid MCF/xenotropic envelope viruses. To date we have demonstrated that the ecotropic host range determining (HRD) region is within the first 157aa of gp70 while the amphotropic HRD region is within the first 88aa of gp70. A further series of experiments are underway to develop MLV based vector systems that will bypass complement mediated inactivation and permit direct injection of gene transfer vectors into the blood stream. The results from these studies will help in the construction of systems for the direct delivery of gene therapy agents to specific human cells.